Clinicogenetic studies of LRRK2 G2019S parkinsonism in Tunisia, North Africa. This is a multicentre consortium between teams in Vancouver, New York, Philadelphia, England and Tunisia to build research capacity and infrastructure at the National Institute of Neurology in Tunis. The reseach project centers about 258 families with parkinsonism in which disease susceptibility is genetically-defined. The studies include clinical assessments, database development and genetic analysis of disease expressivity and penetrance in >1000 asymptomatic and affected family members. James Parkinson (1817) recognised the disease named after him was far more that a late-onset movement disorder. This is the first opportunity to study the disease's natural history, long before movement disorder manifests, and through the lifetime. The outcomes of the project provide the background required for a clinical trial focused on neuroprotection, and have major ramifications for future health care provision in North Africa.
Leucine-rich repeat kinase 2 (LRRK2) in neuronal architecture and membrane dynamics. Work is focused on gaining a mechanistic understanding of the gene, normal and mutant function through a series of domain swapping experiments in LRRK2 knock-out primary neurons, and following up on these findings in vivo. The insight and cell-based systems developed will be useful for drug screening and necessary for future therapeutics.
Nishioka K, Ross OA, Vilariño-Güell C, Cobb SA, Kachergus JM, Mann DM, Snowden J, Richardson AM, Neary D, Robinson CA, Rajput A, Papapetropoulos S, Mash DC, Pahwa R, Lyons KE, Wszolek ZK, Dickson DW, Farrer MJ. Glucocerebrosidase mutations in diffuse Lewy body disease. Parkinsonism Relat. Disord. 17(1):55-7. (2011)
Chung SJ, Armasu SM, Biernacka JM, Lesnick TG, Rider DN, Lincoln SJ, Ortolaza AI, Farrer MJ, Cunningham JM, Rocca WA, Maraganore DM. Common variants in PARK loci and related genes and Parkinson's disease. (2010)
Sossi V, de la Fuente-Fernández R, Nandhagopal R, Schulzer M, McKenzie J, Ruth TJ, Aasly JO, Farrer MJ, Wszolek ZK, Stoessl JA. Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. Mov. Disord. 25(16):2717-23. (2010)
Behrouz B, Vilariño-Güell C, Heckman MG, Soto-Ortolaza AI, Aasly JO, Sando S, Lynch T, Craig D, Uitti RJ, Wszolek ZK, Ross OA, Farrer MJ. Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease. Neurosci. Lett. 486(3):228-30. (2010)
Dächsel JC, Behrouz B, Yue M, Beevers JE, Melrose HL, Farrer MJ. A comparative study of Lrrk2 function in primary neuronal cultures. Parkinsonism Relat. Disord.16(10):650-5. (2010)
Ohshima S, Tsuboi Y, Yamamoto A, Kawakami M, Farrer MJ, Kira J, Shii H.Autonomic failures in Perry syndrome with DCTN1 mutation. Parkinsonism Relat. Disord. 16(9):612-4. (2010)
Jasinska-Myga B, Kachergus J, Vilariño-Güell C, Wider C, Soto-Ortolaza AI, Kefi M, Middleton LT, Ishihara-Paul L, Gibson RA, Amouri R, Yahmed SB, Sassi SB, Zouari M, El Euch G, Ross OA, Hentati F, Farrer MJ. Comprehensive sequencing of the LRRK2 gene in patients with familial Parkinson's disease from North Africa. Mov. Disord.25(13):2052-8. (2010)
Aasly JO, Vilariño-Güell C, Dachsel JC, Webber PJ, West AB, Haugarvoll K, Johansen KK, Toft M, Nutt JG, Payami H, Kachergus JM, Lincoln SJ, Felic A, Wider C, Soto-Ortolaza AI, Cobb SA, White LR, Ross OA, Farrer MJ. Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease. Mov. Disord. 25(13):2156-63. (2010)
Vilariño-Güell C, Wider C, Ross OA, Jasinska-Myga B, Kachergus J, Cobb SA, Soto-Ortolaza AI, Behrouz B, Heckman MG, Diehl NN, Testa CM, Wszolek ZK, Uitti RJ, Jankovic J, Louis ED, Clark LN, Rajput A, Farrer MJ. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics 11(4):401-8. (2010)
Ross OA, Wilhoite GJ, Bacon JA, Soto-Ortolaza A, Kachergus J, Cobb SA, Puschmann A, Vilariño-Güell C, Farrer MJ, Graff-Radford N, Meschia JF, Wszolek ZK.LRRK2 variation and Parkinson's disease in African Americans. Mov. Disord.25(12):1973-6. (2010)
Johansen KK, Hasselberg K, White LR, Farrer MJ, Aasly JO. Genealogical studies in LRRK2-associated Parkinson's disease in central Norway. Parkinsonism Relat. Disord. 16(8):527-30. (2010)
Mayo Clinic Distinguished Investigator – 2008